OVERALL OBJECTIVES: Elucidation of the mechanisms by which histamine stimulates chronotropic and inotropic activity of cardiac muscle and characterization of the receptor involved. 1. Isolated spontaneously beating atrial muscle, driven left atrium and papillary muscle are used to study the mechanical responses to histamine, modification by drugs and environmental conditions (ions, temperature, etc.). 2. Some of the biochemical events initiated by receptor activation (change in calcium flux, CAMP levels, etc.) are studied during receptor stimulation, blockade and in altered metabolic states using radioactive techniques. 3. As study of tissue histamine compartments (cell type and intracellular location) is being performed using fluorescent techniques. The membrane receptor will be visualized using Sepharose bound histamine. Quantitative measurements of tissue histamine levels will be done on tissue extracts. 4. Affinity chromatography will be used in an attempt to isolate the histamine receptor.